Cancer is a disease of heterogeneous genetic origin involving the transformation of one's own cells into a malignant entity. A nearly universal feature of cancer involves the deregulation of various growth and proliferation pathways. This commonality has led to the implementation of two general chemotherapeutic strategies to treat cancer. The first approach inhibits the process of cell division by using agents, such as microtubule inhibitors, DNA alkylating agents, and ionizing radiation that target all rapidly dividing cells. Although these agents are generally efficacious over a broad range of malignancies, the lack of selectivity can unfortunately cause severe dose-limiting side effects, such as alopecia, anemia, and GI discomfort. An alternative strategy is to directly target a specific gene product that is deregulated in a specific type of cancer. An example of this strategy is imatinib (GLEEVAC). By selectively inhibiting the BCR-ABL fusion protein, imatinib is highly specific for chronic myelogenous leukemia (CML) cells with minimal side-effects compared to standard chemotherapy regiment. Unfortunately, imatinib cannot be widely used to treat other types of leukemia. The deficiencies associated with either therapeutic strategy emphasize the need to develop new chemotherapeutic agents that are broad-spectrum and possess a low potential for side-effects.
Although side effects are an obvious complication with chemotherapy, the most serious complication is the development of drug resistance. This type of resistance confers a broad spectrum of cross-resistance to many classes of drugs as they are actively exporting from the cell. This type of resistance, referred to as multi-drug resistance (MDR) phenotype, is exceptionally dangerous since the cancer can become resistant to numerous chemotherapeutic agents.